The proposed research will focus primarily on genes which are linked to the major histocompatibility complex (MHC) of mammals and birds and which can be investigated by electrophoresis or isoelectric focusing. Species with defined MHCs will be screened for polymorphism at gene loci already known to be linked to the MHC of at least one species. Newly discovered polymorphic gene loci will be genetically mapped with respect to the MHC and characterized in regard to their biochemical, physiological, and genetic parameters. Existing MHC-linked markers will also be exploited in investigations of biological parameters pertinent to the characteristics of the markers. For example, polymorphisms of MHC-linked isozyme loci in wild mice will be used to determine if linkage disequilibrium exists among them, as suggested by allelic associations in inbred strains. As another example, the sperm-specific isozyme specified by the Pgk-2 gene, which is linked to the MHC of mice, exists as three allelic forms which will be studied in regard to their effects on male fertility and selection in the haploid phase. The possible presence of antibodies against PGK-2 in vasectomized males will be investigated in mice and rabbits. While it is not feasible to state precisely how newly discovered MHC-linked markers will be exploited until some of their characteristics are defined, one exciting possibility of an MHC-linked marker in chickens would involve studies of gene dosage effects, since chickens trisomic or tetrasomic for the chromosome carrying the MHC are viable. In addition to investigations of MHC-linked gene loci in species with defined MHCs, surveys of isozyme polymorphisms in two American marsupials, Didelphis and Monodelphis, will be performed. The same gene loci will be screened in these species, which do not yet have a defined MHC, but which may have their MHCs characterized soon as they gain popularity as models for developmental studies.